3-16271709-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138381.5(OXNAD1):c.170T>G(p.Val57Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,455,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: OXNAD1 NM_138381.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.393

Genes affected

OXNAD1 (HGNC:25128): (oxidoreductase NAD binding domain containing 1) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06955257).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXNAD1	NM_138381.5	c.170T>G	p.Val57Gly	missense_variant	4/9	ENST00000285083.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXNAD1	ENST00000285083.10	c.170T>G	p.Val57Gly	missense_variant	4/9	1	NM_138381.5	P3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1455728 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4 AN XY: 724098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.170T>G (p.V57G) alteration is located in exon 4 (coding exon 2) of the OXNAD1 gene. This alteration results from a T to G substitution at nucleotide position 170, causing the valine (V) at amino acid position 57 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	13
Dann	Benign	0.82
DEOGEN2	Benign	0.014	T;T;T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.69	T;.;T;.;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.070	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.11	.;B;B;.;.
Vest4		0.22
MutPred		0.34		.;Gain of glycosylation at S56 (P = 0.0283);Gain of glycosylation at S56 (P = 0.0283);.;Gain of glycosylation at S56 (P = 0.0283);
MVP		0.16
MPC		0.045
ClinPred		0.068	T
GERP RS		0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-16313216;